Primary immunodeficiency is a group of diseases that have been increasingly recognized in both children and adults. These diseases, such as Wiskott-Aldrich Syndrome; X-linked hyper IgM syndrome, X-linked lymphoproliferative disease, Severe combined immunodeficiency, X-linked agammaglobulinemia; and Familial hemophagocytic lymphohistiocytosis secondary to perforin 1 and Munc 13-4 mutations, can be difficult to clinically define. Recently, mutation detection has been chosen as the definitive diagnostic criterion for these life-threatening diseases by the Pan-American Group for Immunodeficiency and the European Society for Immunodeficiency.
Wiskott-Aldrich syndrome (WAS) is a rare, X-linked inherited disorder of platelets and immune cells due to deficiency of an intracellular protein, WASP (Wiskott-Aldrich syndrome protein). The Wiskott-Aldrich syndrome protein functions in the normal structure and function of most blood cells. WASP deficiency leads to low platelet counts often associated with small platelet size. Patients exhibit a significant risk of bleeding as well as susceptibility to bacterial, viral, or fungal infections. The differential diagnosis of Wiskott-Aldrich Syndrome includes immune thrombocytopenic purpura (ITP), X-linked congenital neutropenia (XLN), and X-linked thrombocytopenia (XLT). Worldwide, Wiskott-Aldrich Syndrome affects three per million males. Patients with incomplete forms of the disease may survive into adulthood, but most patients die by age 15.
The WASP gene is located on the short arm of the X chromosome at p11.22-p11.23. Previously available mutation detection assays include linkage studies, single-strain confirmation polymorphism (SSCP), and X-inactivation studies. These assays are either less sensitive or time-consuming. Therefore, development of efficient, accurate, sensitive methods of detecting mutations in the genes associated with primary immunodeficiencies, particularly Wiskott-Aldrich syndrome is desirable.